The program outlined in this application has been designed to accelerate the development and commercialization of a Glucagon Mini-Dose Pen to change the paradigm for treatment of moderate hypoglycemia in insulin-using diabetics. This research is directly relevant to the NIDDK which is explicitly interested in the development of innovative technologies for the prevention and treatment of hypoglycemia. The first objective of this program is to manufacture a batch of Xeris' non-aqueous glucagon rescue formulation in pre-filled syringes, which is room-temperature stable and does not require reconstitution. These clinical supplies will be put on a long-term stability study in preparation for conducting a Phase 2a clinical trial. The second objective of this program is to conduct a Phase 2a clinical study in healthy, type 1 diabetics that allows for patient-friendly administration of mini-doses of glucagon In this context, healthy refers to well controlled/managed insulin-using T1D patients without clinical evidence of chronic complications such as nephropathy, retinopathy, neuropathy, etc. The clinical trial will demonstrate the dose-response of glucagon mini-doses in terms of the ability to effectively raise blood glucose levels of treated patients. Successful completion of the clinical program will demonstrate the safety, pharmacokinetics and initial efficacy of glucagon mini-doses for use in treatment of moderate hypoglycemia. The third objective is to manufacture a GLP batch of non-aqueous glucagon to demonstrate compatibility in a standard 3 mL drug cartridge format designed for use in a multi-dose pen. Accomplishment of this specific aim will demonstrate a formulation that is stable for at least one year at room temperature, can be delivered as multiple mini-doses, can be used in a preclinical study, and can ultimately be carried forward into a clinical supplies manufacturing program. The formulation will be tested to demonstrate initial stability and a preclinical study will demonstrate long-term safety in a rabbit model. The data collected in this effort will provide a package for a longer-term Phase 2b human clinical study with a commercial product.